78 / 86
temperature, and no microbial growth was
noted. The same results were found in eight vials
of this product kept refrigerated for 15 days after
reconstitution.
52
Dilution Issues
There is considerable discussion about the effect of
dilution of BoNTs on clinical effect, duration, or
diffusion. The package insert for onabotulinumtox-
inA and incobotulinumtoxinA recommends dilution
of 100 U in 1 to 8mL of saline (12.5–100 U/mL).
15,19
For abobotulinumtoxinA, 300 U can be diluted in
0.6 to 2.5mL (120–500 U/mL).
16
Rimabotulinum-
toxinB can be diluted as much as 6 times using
normal saline, but a more-concentrated solution
cannot be generated.
43,51,61,62
Many authors believe that higher dilutions could be
associated with greater risk of diffusion to unwanted
sites,
12,63–68
unsatisfactory results, or shorter dura-
tion, but this is not unanimous in the literature.
To better understand the effect of dilution on diffu-
sion, side effects, and treatment success, studies were
reviewed according to indication.
Facial Muscles
Cosmetic Indications
Expert consensus panels for cosmetic indications
recommend dilutions between 1 and 3mL of saline
for onabotulinumtoxinA
22
and between 1.5 and
2.5mL for abobotulinumtoxinA.
32,69
In 1996, a group reported the use of large volumes os
low dose BoNTA
70
, with dilutions of 5 and 10 mL of
onabotulinumtoxin A. Two years later, Fulton
71
compared injections to one side of the face with
dilutions of 10mL with those of 15 and 20mL/vial
in 10 individuals. He noted that the 10- and 15-mL
dilutions were efficacious but had shorter duration.
Frequent retreatments were needed to maintain
long-term results. He also reported that a great
number of individuals were resistant to the toxin, so
higher dilutions are no longer recommended.
Hankins and colleagues evaluated 46 patients
with glabellar wrinkles injected with different
concentrations of onabotulinumtoxinA ranging
from 10 and 100 U/mL for up to 21 weeks. They
found no differences in effect or duration of
treatment, but larger volumes were associated
with greater discomfort.
72
Le Louarn
41
described his dilution technique, in
which large volumes of saline mixed with epineph-
rine were added (2 or 3 times the initial volume) to
abobotulinumtoxinA and onabotulinumtoxinA. This
diluted toxin was used to treat areas of the face
where a higher spread, in his opinion, would be
beneficial, such as the frontalis, platysma, and
orbicularis oculi muscles.
In a study with 10 volunteers,
73
Hsu and colleagues
injected the forehead with 5 U of onabotulinumtox-
inA diluted to 20 (5mL) or 100 U/mL (1mL). They
found that higher-volume injections resulted in
greater diffusion and a larger affected area and sug-
gested that muscle contraction influences the pattern
of toxin spread.
Carruthers and colleagues studied the effect of dif-
ferent dilutions of onabotulinumtoxinA in the
treatment of glabellar rhytides. They followed 80
patients treated with dilutions of 10, 20, 33.3, or
100 U/mL in the glabella (20/group) for 48 weeks.
There were no statistical differences in treatment
success or adverse effect reports, although six cases
of eyebrow ptosis were
F
all in the higher-dilution
group.
74
Another trial enrolled 20 patients treated for lateral
orbital rhytides observed for 90 days. Two different
dilutions of onabotulinumtoxinA were used (20 and
100 U/mL); no statistically significant differences
were detected in response or adverse effects, even
though the lower-dilution group showed a slightly
better response.
75
DERMATOLOG I C SURGERY
HANDL I NG BOTUL I NUM TOX I NS